R. Steininger

Current value of intraoperative sonography during surgery for hepatic neoplasms

Noninvasive liver imaging has developed rapidly resulting in increased accuracy for detecting primary and secondary hepatic tumors. Intraoperative ultrasonography (IOUS) was commonly considered to be the gold standard for liver staging, but the current value of IOUS is unknown in view of more sophisticated radiologic tools. The purpose of this prospective study was to evaluate the impact of IOUS on the treatment of 149 patients undergoing liver surgery for malignant disease (colorectal metastasis, 61 patients; hepatoma, 52 patients; other hepatic malignant tumors, 36 patients). The sensitivities of computed tomography (CT), helical CT, magnetic resonance imaging, and IOUS in patients with colorectal metastases were 69.2%, 82.5%, 84.9%, and 95.2% in a segment-by-segment analysis; in patients with hepatoma their sensitivities were 76.9%, 90.9%, 93.0%, and 99.3%; and in patients with other hepatic malignancies they were 66.7%, 89.6%, 93.3%, and 98.9%, respectively. Additional malignant lesions (AMLs) were first detected by inspection and palpation in 20 patients (13.4%). In another 18 patients (12.1%) IOUS revealed at least one AML. Overall, the findings obtained only by IOUS changed the surgical strategy in 34 cases (22.8%). It was concluded that IOUS, having undergone some refinement as well, still has immense diagnostic value in hepatectomy candidates. Frequently avoiding palliative liver resection and occasionally disproving unresectability as assessed by preoperative imaging, IOUS still has a significant impact on surgical decision making and should still be considered the gold standard.RésuméOn a récemment assisté à une amélioration importante dans la précision de la détection des tumeurs primitives et secondaires du foie par l’imagerie non-invasive. L’échographie peropératoire (EPO) a été considérée comme l’examen de référence («gold standard») dans le Staging du foie, mais la valeur de l’EPO est discutée à présent en raison de l’apparition d’investigations radiologiques plus sophistiquées. Le but de cette étude prospective a été d’évaluer l’impacte de l’EPO au cours d’une résection hépatique pour maladie maligne chez 149 patients (métastases d’origine colorectale: 61 patients; carcinome hépatocellulaire: 52 patients; autres tumeurs hépatiques malignes: 36 patients). Chez les patients ayant des métastases d’origine colorectale, la sensibilité de la tomodensitométrie simple (TDM), de la tomodensitométrie hélicoïdale (TDMh), de la résonance magnétique (RM) et l’EPO a été de 69.2%, 82.5%, 84.9% et 95.2% dans une analyse du foie segment par segment. Chez les patients porteurs de carcinome hépatocellulaire, la sensibilité de ces différentes méthodes était, respectivement, de 76.9%, 90.9%, 93% et 99.3%; chez les patients ayant d’autres tumeurs malignes du foie, la sensibilité était, respectivement, de 66.7%, 89.6%, 93.3% et 98.9%. D’autres lésions malignes ont été détectées à l’inspection et à la palpation chez 20 patients (13.4%). De plus, chez 18 autres patients (12.1%), l’EPO a décelé au moins une lésion maligne supplémentaire. Globalement, les données obtenues par l’EPO ont changé la stratégie chirurgicale dans 34 cas (22.8%). On conclue que l’EPO, grâce à quelques raffinements, a toujours une immense valeur diagnostique pour les candidats à l’hépatectomie. En évitant à certains patients une résection palliative, et en permettant, de temps à autre, une résection jugée impossible par les investigations préopératoires, l’EPO garde un impacte significatif sur la décision chirurgicale et devrait continuer à être le «gold standard».ResumenEl rápido desarrollo de los métodos no invasivos ha conferido una mayor precisión diagnóstica de los tumores hepáticos tanto primarios como secundarios. La ecografÍa intraoperatoria (IOUS) se consideró como el mejor método diagnóstico para la estadificación hepática, pero en la actualidad, su valor está en entredicho ante los nuevos y sofisticados estudios radiológicos. El objetivo de este estudio prospectivo fue evaluar el valor de la IOUS en el tratamiento quirúrgico de 149 pacientes con neoplasias malignas de hÍgado (metástasis colorrectales n=61; hepatomas n=52; otros tumores hepáticos malignos n=36). El análisis secuencial segmentario demostró en pacientes con metástasis colorrectales una sensibilidad para la tomografÍa axial o helicoidal computarizada (CT y hCT) del 69.2% y 82.5%, para la resonancia magnética nuclear (MR) del 84.9% y para la IOUS del 95.2%. En pacientes con hepatomas la sensibilidad de estos métodos fue del 76.9%, 90.9%, 93% y 98.9%. En 20 pacientes (13.4%) lesiones malignas adicionales (AML) se diagnosticaron por inspección y palpación. En otros 18 pacientes (12.1%) la IOUS fue capaz de detectar al menos una AML. En 34 casos (22.8%) el conjunto de hallazgos obtenidos exclusivamente con la IOUS propició un cambio de estrategia quirúrgica. En conclusión, la IOUS, con sus recientes mejoras, sigue teniendo un inmenso valor diagnóstico para aquellos que son candidatos a una hepatectomÍa. Previene, con frecuencia, las resecciones hepáticas paliativas y, ocasionalmente, contradice el diagnóstico de irresecabilidad obtenido con otros medios diagnósticos. La IOUS sigue teniendo un importante valor a la hora de establecer una decisión quirúrgica y continúa siendo el mejor método diagnóstico.

Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver

BACKGROUND/AIMS Thrombocytopenia secondary to cirrhosis of the liver and portal hypertension is a well-known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly centering on splenic sequestration and destruction of platelets, have failed to solve the problem so far. METHODS Peripheral platelet count and thrombopoietin levels in human plasma were measured in 28 patients with cirrhosis of the liver. Seven of those patients underwent orthotopic liver transplantation and five patients portal decompression by transjugular intrahepatic portosystemic shunt. Thrombopoietin plasma levels were followed for 14 days after the interventions. RESULTS No measurable thrombopoietin was detectable in the plasma of 28 thrombocytopenic patients with cirrhosis of the liver, in contrast to thrombocytopenic patients without liver disease. Seven of these patients with cirrhosis underwent orthotopic liver transplantation, resulting in a rise of thrombopoietin levels within 2 days after transplantation. The rise in platelet number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin levels returned to levels below the limit of detection. Five patients with thrombocytopenia, who underwent only decompression of portal hypertension, showed no rise in either thrombopoietin levels or platelet count. CONCLUSIONS Thrombocytopenia associated with liver disease may at least in part be attributable to inadequate thrombopoietin production in the failing liver.

Radical Surgical Therapy of Abdominal Cystic Hydatid Disease: Factors of Recurrence

Abstract. A series of 74 consecutive patients (48 women, 26 men) were operated for abdominal hydatid disease between June 1949 and December 1995. The patients ranged in age from 15 to 81 years (median 49 years). In 69 cases only the liver was affected; two patients had concomitant extrahepatic disease (one spleen, one spleen and lung), and 3 had cysts in the spleen only. Cysts were multiple in 11 patients and calcified in 24. Conservative surgical procedures were used for 22 cysts in 20 patients [open partial (n= 3), open total (n= 6), closed total cystectomy (n= 9), marsupialization (n= 2), drainage (n= 2)] and radical surgical procedures for 72 cysts in 54 patients [pericystectomy (n= 41), wedge liver resection or hemihepatectomy (n= 25), splenectomy (n= 5), radical resection of a lung cyst (n= 1)]. Altogether 37 patients (50%) were given perioperative antihelmintic chemotherapy with mebendazole (18 patients) or albendazole (19 patients). Operative mortality rates were 5.0% after conservative surgery and 1.8% after radical surgery. Morbidity rates were 25.0% following conservative surgery and 24.1% following radical surgery. Antihelmintic therapy was well tolerated by all but five patients. All side effects were entirely reversible. Among the 74 patients, 60 (81.0%) were available for long-term follow-up (median 7.2 years; range 2.0–47.0 years). Recurrence of disease was seen in 9 of 60 patients at an interval of 3 months to 20 years from the first operation. The rate of recurrence was significantly lower after radical surgical procedures (p= 0.03) and after closed removal of the cyst (p= 0.04).

Analysis of hepatic resection of metastasis originating from gastric adenocarcinoma

Few patients with metastatic gastric cancer have disease that is amenable to curative surgery. Thus far, little is known about liver surgery for metastases arising from gastric adenocarcinoma and prognostic factors. Of 73 patients operated on between 1980 and 1999 for noncolorectal, non-neuroendocrine hepatic metastases, 15 underwent liver resection for gastric adenocarcinoma metastasis. Ten patients underwent synchronous hepatic resection and five underwent metachronous hepatic surgery after a median diseasefree interval of 10 months (range 6.1 to 47.3 months). None of the patients died within the first 30 days after surgery, and the in-hospital mortality rate was 6.7%. Among patients in the synchronous group, 26.7% experienced major complications mainly associated with gastric surgery. Overall median survival was 8.8 months (range 4 to 51 months); two patients survived more than 3 years. Univariate analysis reealed that the appearance of liver metastasis synchronous vs. metachronous), the distribution of liver metastases (unilobar vs. bilobar), and the primary tumor site (proximal vs. distal) were marginally signifiant predictive factors regarding overall survival. Because of its high morbidity, synchronous liver resecion for metastases originating from gastric adenocarcinoma is rarely followed by survival longer than 2 years. Primary tumor localization within the proximal third of the stomach and bilobar liver involvement appear to be predictive of poor outcome. On the other hand, curative resection of metachronous liver metastases may allow long-term survival in selected patients.

Organ survival after primary dysfunction of liver grafts in clinical orthotopic liver transplantation

Abstract In a retrospective analysis of 632 orthototopic liver transplant procedures performed between 1982 and 1997, the incidence of primary dysfunction (PDF) of the liver and its influence on organ survival were studied. Graft function during the first 3 postoperative days was categorized into four groups: (1) good (GOT max < 1000 U/l, spontaneous PT > 50 %, bile production > 100 ml/day); (2) fair (GOT 1000‐2500 U/l, clotting factor support < 2 days, bile < 100 ml/day); (3) poor (GOT > 2500 U/l, clotting factor support > 2 days, bile < 20 ml/day); (4) primary non‐function (PNF; retransplantation required within 7 days). The aim of this study was to evaluate graft survival comparing organs with PDF (poor function) and PNF vs organs with initial good or fair function. After a median follow‐ up of 45 months, initially good and fair function of liver grafts resulted in a significantly better long‐term graft survival compared with grafts with initially poor function or primary non‐function (if re‐transplanted) (P < 0.01). The Cox model revealed primary function as a highly significant factor in the prediction of long‐term graft survival (P < 0.0001). We conclude that these results confirm the hypothesis that primary graft function is of major importance for the long‐term survival of liver transplants. Patients with a poor primary function have the worst survival prognosis, which leads to the interpretation that these patients may be candidates for early retransplantation.

Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus)

ZusammenfassungDas durch MDMA (Ecstasy) ausgelöste fulminante Leberversagen weist — insbesondere exzessive Mortalität auf. Die notfallmäßige Lebertransplantation ist die einzige etablierte Behandungsform. Wir berichten über einen jungen Patienten mit kombinierter Ecstasy/Kokain-Intoxikation mit akutem Leberversagen, Rhabdomyolyse, Septuminfarkt und Multiorganversagen. Die Lebertransplantation wurde aufgrund des rezenten intravenösen Drogenkonsums trotz Erfüllung der Transplantationskriterien abgelehnt. Infolge massiver Hyperammoniämie (318 μmol/l) und refraktärer zerebraler Herniation begannen wir eine kontinuierliche extrakorporale Behandlung mit dem FPSA-Prometheus System, welches adsorptive und dialytische Toxinentfernung kombiniert. Nach rascher Normalisierung des Ammoniakwertes kam es innerhalb von 4 Tagen zu Einsetzen von Leberregeneration und vollständiger Rückbildung des Hirnödems. Der Patient konnte das Krankenhaus nach Rehabilitation mit geringgradigen neurologischen Folgeerscheinungen verlassen. Effiziente extrakorporale Detoxifikation kann durch eine rasche Normalisierung von Hyperammoniämie und Hirnödem bei Ecstasy/Kokaininduziertem akutem Leberversagen eine therapeutische Option darstellen.SummaryEcstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 μmol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.

The importance of the effect of underlying disease on rejection outcomes following orthotopic liver transplantation

Despite major advances in immunopharmacology, virtually all patients receive the same center-specific immunosuppressive regimen following orthotopic liver transplantation (OLT). The present analysis was performed on the hypothesis that the original disease representing the indication for OLT leads to a different initial immunological situation of the patient. The type of original disease might therefore be a predisposing factor for acute rejection episodes and influence graft and patient survival. From January 1988 to July 1994, 34 patients received OLT at our institution for end-stage primary biliary cirrhosis (group 1) and 66 patients for end-stage alcoholic cirrhosis (group 2). Overall survivals at 1 and 5 years in group 1 versus group 2 were 67% versus 80% and 50% versus 68%, respectively (P<0.04). Retransplantation was performed in 21% of patients from group 1 and in 6% from group 2. The estimated risk for freedom from acute rejection amounts to 38% in group 1 compared with 59% in group 2 (P<0.02). Multivariate regression analysis of potential risk factors identified only the underlying disease as independent predictor. Analysis of cumulative rates of clinically relevant rejection episodes stratified by group revealed 0.29 and 0.05 episodes per patient at one month and 0.80 and 0.06 at six months (P<0.009) respectively. In our clinical experience it was possible to confirm the hypothesis that the underlying disease is the reason for a significantly different incidence of acute rejection episodes and that it subsequently influences graft and patient survival. This approach to an individually adapted immunosuppressive therapy should be taken into consideration and other appropriate parameters investigated.

Austrian consensus on the definition and treatment of portal hypertension and its complications (Billroth II)

SummaryIn November 2004, the Austrian Society of Gastroenterology and Hepatology (ÖGGH) held for the first time a consensus meeting on the definitions and treatment of portal hypertension and its complications in the Billroth-Haus in Vienna, Austria (Billroth I-Meeting). This meeting was preceded by a meeting of international experts on portal hypertension with some of the proponents of the Baveno consensus conferences (http://www.oeggh.at/videos.asp). The consensus itself is based on the Baveno III consensus with regard to portal hypertensive bleeding and the suggestions of the International Ascites Club regarding the treatment of ascites. Those statements were modified by new knowledge derived from the recent literature and also by the current practice of medicine as agreed upon by the participants of the consensus meeting. In October 2011, the ÖGGH organized the second consensus meeting on portal hypertension and its complications in Vienna (Billroth II-Meeting). The Billroth II-Guidelines on the definitions and treatment of portal hypertension and its complications take into account the developments of the last 7 years, including the Baveno-V update and several key publications.ZusammenfassungIm November 2004 hielt die Österreichische Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) den ersten Konsensus über die Definitionen und die Therapie der Portalen Hypertension und ihrer Komplikationen im Billroth-Haus in Wien, Österreich ab (Billroth I Meeting). Diesem Treffen ging ein internationales Expertenmeeting über die Portale Hypertension mit einigen wichtigen Proponenten der Baveno Konsensus-Konferenzen vorraus (http://www.oeggh.at/videos.asp). Der Konsensus selber basiert auf dem Baveno III Konsensus im Hinblick auf die portal-hypertensive Blutung und den Vorschlägen des International Ascites Club in Hinblick auf die Therapie des Aszites. Deren Aussagen wurden mit neuen Erkenntnissen aus der rezenten Literatur und auch entsprechend der praktischen Erfahrung der Teilnehmer des Konsensus-Treffens modifiziert. Im Oktober 2001 organisierte die ÖGGH das zweite Konsensus Treffen über die portale Hypertension und ihrer Komplikationen (Billroth II Meeting). Die Billroth II Leitlinien über die Definitionen und die Therapie der Portalen Hypertension und ihrer Komplikationen lassen die Entwicklungen der letzten 7 Jahre inklusive des Baveno V Updates und etlicher Schlüsselpublikationen mit einfließen und stellen den neuen Standard im Management der Portalen Hypertension in Österreich dar.

Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation

BACKGROUND The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This deficiency is possibly related to pulmonary hypertension and reduced hepatic blood flow, which are commonly observed in the immediate reperfusion period. The aim of this study was to evaluate the impact of L-arginine supplementation on metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs. METHODS Thirteen pig OLTs (control group, n=6; arginine group, n=7) were performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before liver explantation) and also into the recipients (over a period of 3 hr from the beginning of the reperfusion period). At the end of the experimental study, the pigs were killed with an overdose of potassium. RESULTS In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%). Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21 micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to 116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and nitrate. Administration of L-arginine in the donor pigs did not produce any systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into the recipient pigs improved cardiac performance (increase in heart rate [+61%, P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen consumption (+65%, P=0.003), reduced pulmonary vascular resistance index (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body temperature during the reperfusion period (P=0.007). CONCLUSIONS From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.

Detection of graft nonfunction after liver transplantation by assessment of indocyanine green kinetics

I ndocyanine green dye (ICG) has been used in tests for a global measure of liver perfusion and excretory function for more than three decades (1) and has shown good correlation with the severity of hepatic disease as well as with outcome in liver transplant recipients (2-5). We report a case of the early detection of graft nonfunction after orthotopic liver transplantation (OLT) using a bedside monitoring device for fiberoptic assessment of ICG plasma disappearance rate (ICG PDR) (normal value 20%-30%) (2) in a 43-yr-old woman who underwent OLT because of cholangiocellular carcinoma. Retransplantation was performed, and the patient was dismissed from the hospital 3 wk after the first OLT.